A Genome-Scale Insight into the Effect of Shear Stress During the Fed-Batch Production of Clavulanic Acid by Streptomyces Clavuligerus

dc.contributor.authorGómez-Ríos, David
dc.contributor.authorLópez-Agudelo, Victor A.
dc.contributor.authorRamírez-Malule, Howard
dc.contributor.authorNeubauer, Peter
dc.contributor.authorJunne, Stefan
dc.contributor.authorOchoa, Silvia
dc.contributor.authorRíos-Estepa, Rigoberto
dc.date.accessioned2020-12-10T07:43:01Z
dc.date.available2020-12-10T07:43:01Z
dc.date.issued2020-08-19
dc.date.updated2020-09-02T23:22:49Z
dc.description.abstractStreptomyces clavuligerus is a filamentous Gram-positive bacterial producer of the β-lactamase inhibitor clavulanic acid. Antibiotics biosynthesis in the Streptomyces genus is usually triggered by nutritional and environmental perturbations. In this work, a new genome scale metabolic network of Streptomyces clavuligerus was reconstructed and used to study the experimentally observed effect of oxygen and phosphate concentrations on clavulanic acid biosynthesis under high and low shear stress. A flux balance analysis based on experimental evidence revealed that clavulanic acid biosynthetic reaction fluxes are favored in conditions of phosphate limitation, and this is correlated with enhanced activity of central and amino acid metabolism, as well as with enhanced oxygen uptake. In silico and experimental results show a possible slowing down of tricarboxylic acid (TCA) due to reduced oxygen availability in low shear stress conditions. In contrast, high shear stress conditions are connected with high intracellular oxygen availability favoring TCA activity, precursors availability and clavulanic acid (CA) production.en
dc.identifier.eissn2076-2607
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/12165
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-11039
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc570 Biowissenschaften; Biologiede
dc.subject.otherStreptomycesen
dc.subject.othergenome-scale modelen
dc.subject.otherflux balance analysisen
dc.subject.otherclavulanic aciden
dc.subject.otherStreptomyces clavuligerusen
dc.subject.otherTCA cycleen
dc.subject.othersecondary metabolismen
dc.subject.othermetabolic modelingen
dc.subject.otherantibioticen
dc.titleA Genome-Scale Insight into the Effect of Shear Stress During the Fed-Batch Production of Clavulanic Acid by Streptomyces Clavuligerusen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber1255en
dcterms.bibliographicCitation.doi10.3390/microorganisms8091255en
dcterms.bibliographicCitation.issue9en
dcterms.bibliographicCitation.journaltitleMicroorganismsen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume8en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Bioverfahrenstechnikde
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Bioverfahrenstechnikde
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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